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首页> 外文期刊>Physical Review X >Polymer model with Epigenetic Recoloring Reveals a Pathway for the de novo Establishment and 3D Organization of Chromatin Domains
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Polymer model with Epigenetic Recoloring Reveals a Pathway for the de novo Establishment and 3D Organization of Chromatin Domains

机译：具有表观遗传着色的聚合物模型揭示了染色质域从头建立和3D组织的途径

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One of the most important problems in development is how epigenetic domains can first be established, and then maintained, within cells. To address this question, we propose a framework that couples three-dimensional chromatin folding dynamics to a “recoloring” process modeling the writing of epigenetic marks. Because many intrachromatin interactions are mediated by bridging proteins, we consider a “two-state” model with self-attractive interactions between two epigenetic marks that are alike (either active or inactive). This model displays a first-order-like transition between a swollen, epigenetically disordered phase and a compact, epigenetically coherent chromatin globule. If the self-attraction strength exceeds a threshold, the chromatin dynamics becomes glassy, and the corresponding interaction network freezes. By modifying the epigenetic read-write process according to more biologically inspired assumptions, our polymer model with recoloring recapitulates the ultrasensitive response of epigenetic switches to perturbations and accounts for long-lived multidomain conformations, strikingly similar to the topologically associating domains observed in eukaryotic chromosomes.
机译：发展中最重要的问题之一是如何先在细胞内建立表观遗传域，然后再进行维持。为了解决这个问题，我们提出了一个框架，该框架将三维染色质折叠动力学与建模表观遗传标记的“重新着色”过程相结合。因为许多染色质内相互作用是由桥蛋白介导的，所以我们考虑“两个状态”模型，两个相似的表观遗传标记（有活性或无活性）之间具有自吸引相互作用。该模型在肿胀的表观遗传无序相和紧密的表观遗传相干染色质小球之间显示出一阶过渡。如果自吸引强度超过阈值，则染色质动力学将变得玻璃状，并且相应的相互作用网络将冻结。通过根据更多受生物学启发的假设修改表观遗传读写过程，我们的带有重着色的聚合物模型概括了表观遗传开关对扰动的超灵敏响应，并解释了长期存在的多域构象，这与真核染色体中观察到的拓扑关联域极为相似。

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